Transcription-independent expression of PKMζ in the anterior cingulate cortex contributes to chronically maintained neuropathic pain.

Abstract

Protein kinase M ζ is well known for its role in maintaining memory and pain. Previously, we revealed that the activation of protein kinase M ζ in the anterior cingulate cortex plays a role in sustaining neuropathic pain. However, the mechanism by which protein kinase M ζ is expressed in the anterior cingulate cortex by peripheral nerve injury, and whether blocking of protein kinase M ζ using its inhibitor, zeta inhibitory peptide, produces analgesic effects in neuropathic pain maintained chronically after injury, have not previously been resolved. In this study, we show that protein kinase M ζ expression in the anterior cingulate cortex is enhanced by peripheral nerve injury in a transcription-independent manner. We also reveal that the inhibition of protein kinase M ζ through zeta inhibitory peptide treatment is enough to reduce mechanical allodynia responses in mice with one-month-old nerve injuries. However, the zeta inhibitory peptide treatment was only effective for a limited time.

• Authors: Hyoung-Gon Ko, Sanghyun Ye, Dae-Hee Han, Pojeong Park, Chae-Seok Lim, Kyungmin Lee, Min Zhuo, Bong-Kiun Kaang
• Journal: Molecular pain (Mol Pain) 2018 Jan-Dec Vol. 14 Pg. 1744806918783943 ISSN: 1744-8069 [Electronic] United States
• PMID: 29923456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell-Penetrating Peptides
• Lipopeptides
• Receptors, AMPA
• zeta-inhibitory peptide
• Protein Kinase C
• glutamate receptor ionotropic, AMPA 2

Topics

• Animals
• Cell-Penetrating Peptides
• Chronic Pain (enzymology, genetics, pathology)
• Gyrus Cinguli (enzymology, pathology)
• Lipopeptides (pharmacology)
• Long-Term Potentiation
• Male
• Mice, Inbred C57BL
• Neuralgia (enzymology, genetics, pathology)
• Peripheral Nerves (pathology)
• Protein Kinase C (metabolism)
• Receptors, AMPA
• Synapses (metabolism)
• Transcription, Genetic (drug effects)